Anti angiogenic therapy has tremendous potential for the treatment of cancer. Several anti-angiogenic agents currently in clinical trials are large protein domains, which face several challenges for clinical development. Proteins used for anti-angiogenic therapy typically require large and frequent doses, which make them too costly to be commercially feasible. A possible solution lies in identifying the minimal regions of an anti-angiogenic protein, then optimizing lead compounds based on these minimized regions. We have identified and patented a novel multi-domain protein which has the ability to inhibit angiogenesis and tumor growth, and have discovered its receptor in activated endothelial cells. The anti-angiogenic activity of this protein is localized in a single domain and a pentapeptide within this domain retains anti-angiogenic activity. In this application, we propose to corroborate and investigate further the ability of this domain to inhibit tumor growth in vivo. In parallel, we will also carry out optimization of the pentapeptide with the aim of obtaining a lead compound with appropriate affinity and potency. Further optimization would be carried out during the Phase II period of this SBIR, with the goal of developing a clinical candidate based on this modified pentapeptide. PROPOSED COMMERCIAL APPLICATIONS: We propose a novel and widely applicable new drug for the treatment of cancer. The need for more effective cancer therapy is readily apparent, as more than 15 million in the U.S. alone contract some type of cancer each year. This represents a potential market of $10 billion per year.